A novel treatment for rare disease Friedreich ataxia using p38 or MK2 kinase inhibitors
Friedreich ataxia (FA) is an autosomal recessive, inherited neuro- and cardio-degenerative disorder characterized by progressive ataxia of all four limbs, skeletal deformities, and hypertrophic cardiomyopathy. FA is the most prevalent inherited ataxia, affecting about 1 in 50,000 people in the United States. The estimated carrier prevalence is 1:110.
Onset of symptoms can vary from childhood to adulthood with most patients being confined to a wheelchair by their late 20s. Myocardial failure and/or arrhythmias are the most common cause of premature death. It is commonly believed that FA is caused by mitochondrial dysfunction caused by the decreased expression of the protein Frataxin.
Currently there are no approved drugs to treat FA and the resultant disability, prolong the life of a FA patient, or cure the disorder.
Work in the Wilson Lab led to a surprising discovery that p38 MAP kinase inhibitors (many of which are in clinical trials for various indications) rescue disease phenotypes of cells affected by FA. This suggests that the p38 kinase (or MK2) can be possible targets for therapeutic intervention in Friedreich ataxia.rules, are highly specific to FA, and are active in the low nanomolar range. Several optimized modifications of the lead compounds have been generated.
- A number of p38 kinase inhibitors are being tested in clinical trials for various indications
- Regulatory fast-track: FA is a FDA designated orphan disease with no approved treatment
- Access to the expertise and resources of Wilson’s lab (see Inventor’s Bio)
Robert Wilson M.D., Ph.D. is a world-renowned expert studying Friedreich ataxia for over 18 years, both in clinical and lab research settings. Dr. Wilson is co-Director of the CHOP-UPenn Center of Excellence for Friedreich’s ataxia Research which involves 13 centers in 5 countries. The Center sees more FA patients than any other center in the world and is actively developing biomarkers, clinical protocols, and ataxia scales for use as Phase III endpoints. Dr. Wilson was the Scientific Director of Friedreich’s Ataxia Research Alliance for 7 years and currently serves on the Medical Research Advisory Board for the National Ataxia Foundation. The Wilson lab has developed, and/or utilizes, most of the models of the disorder, has the reagents and expertise to measure all aspects of FA biochemistry, and is actively collaborating with FA researchers throughout the world.
- Sponsored research
Cotticelli et al. Sci Rep 2018, 8: 5007
Docket # 15-7449
Keywords: therapeutic, drug discovery, orphan disease